Metastatic variant sublines of the murine RAW117 large cell lymphoma or lymphosarcoma have been established in vitro by sequential cycles of harvesting of liver tumor nodules after intravenous inoculation of tumor cell suspensions into syngeneic BALB/c mice. After five and ten in vivo selections for liver colonization, variant sublines RAW117-H5 and -H10, respectively, were established, and these formed significantly more surface liver tumors than the parental RAW117-P line. RAW117 sublines were tested for their abilities to adhere to embryonic mouse liver or brain cells in an in vitro cell-cell adhesion assay. Liver colonizing RAW117-H10 cells adhered with greater selectivity to liver cells than to brain cells. Parental RAW117-P cells were more homotypically adhesive, but they were nonselective in their organ cell adhesion properties. We examined RAW117 cells for the presence of liver cross-reactive antigens using polyclonal xenoantibody preparations directed against embryonic murine liver cells. These antibody preparations block organ-specific homotypic adhesion of embryonic murine liver cells in vitro. The amount of fetal liver antigen(s) expressed on RAW117 sublines correlated with liver colonization potentials (H10 greater than H5 greater than P) in quantitative absorption assays. Treatment of the highly metastatic RAW117-H10 subline with polyclonal anti-embryonic murine liver F(ab')2 or Fab' antibody fragments had no effect on RAW117-H10 cell viability or growth in vitro or in vivo, but inhibited liver colonization (median liver tumor colonies reduced from greater than 200 to 0) and prolonged life expectancy. In contrast, pretreatment of RAW117-H10 cells with polyclonal anti-H-2 did not modify the in vivo biologic properties of these metastatic cells.